Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our prior analysis of gene expression in tumor endothelium led to the identification of a G-protein coupled receptor called TEM5. Few GPCRs have been identified in angiogenic blood vessels, yet approximately half of all marketed drugs target this group of receptors. In an attempt to understand the role of TEM5 in angiogenesis and its importance for tumor growth, we have embarked upon a hunt for its physiological ligand. We are also using various in vitro assays in order to unravel its function and determine if it is able to interact with various integrins at the cell surface.